Hong Kong consensus recommendations on the management of pancreatic ductal adenocarcinoma.

This project was undertaken to develop the first set of consensus statements regarding the management of pancreatic ductal adenocarcinoma (PDAC) in Hong Kong, with the goal of providing guidance to local clinicians. A multidisciplinary panel of experts discussed issues surrounding current PDAC management and reviewed evidence gathered in the local context to propose treatment recommendations. The experts used the Delphi approach to finalise management recommendations. Consensus was defined as ≥80% acceptance among all expert panel members. Thirty-nine consensus statements were established. These statements cover all aspects of PDAC management, including diagnosis, resectability criteria, treatment modalities according to resectability, personalised management based on molecular profiling, palliative care, and supportive care. This project fulfils the need for guidance regarding PDAC management in Hong Kong. To assist clinicians with treatment decisions based on varying levels of evidence and clinical experience, treatment options are listed in several consensus statements.

Acute kidney injury following hepatectomy and its impact on long-term survival for patients with hepatocellular carcinoma.

BACKGROUND: Acute kidney injury (AKI) is increasingly being recognized after hepatectomy. This study aimed to identify factors predicting its occurrence and its impact on long-term outcome among patients with hepatocellular carcinoma (HCC). METHODS: This was a retrospective analysis of the incidence of AKI, factors predicting its occurrence, and its impact on patients undergoing hepatectomy between September 2007 and December 2018. A subgroup analysis included patients with histologically proven HCC. RESULTS: The incidence of AKI was 9.2 per cent in 930 patients. AKI was associated with increased mortality, morbidity, posthepatectomy liver failure (PHLF), and a longer hospital stay. On multivariable analysis, study period December 2013 to December 2018, diabetes mellitus, mean intraoperative BP below 72.1 mmHg, operative blood loss exceeding 377ml, high Model for End-Stage Liver Disease (MELD) score, and PHLF were predictive factors for AKI. Among 560 patients with HCC, hypertension, BP below 76.9 mmHg, blood loss greater than 378ml, MELD score, and PHLF were predictive factors. The 1-, 3-, and 5-year overall survival rates were 74.1, 59.2, and 51.6 per cent respectively for patients with AKI, and 91.8, 77.9, and 67.3 per cent for those without AKI. Corresponding 1-, 3-, and 5-year disease-free survival rates were 56.9, 42.3, and 35.4 per cent respectively in the AKI group, and 71.7, 54.5, and 46.2 per cent in the no-AKI group. AKI was an independent predictor of survival in multivariable analysis. CONCLUSION: AKI is associated with longer hospital stay, and higher morbidity and mortality rates. It is also associated with shorter long-term survival among patients with HCC. To avoid AKI, control of blood loss and maintaining a reasonable BP (72-77 mmHg) during hepatectomy is important.

Robotic versus laparoscopic hepatectomy: application of the difficulty scoring system.

BACKGROUND: The development of robotic system may help to relieve the difficulties encountered during laparoscopic hepatectomy. A difficulty scoring system (DSS) was developed to assess the difficulty of various laparoscopic liver resection procedures. The aim of this study is to explore if the DSS is applicable in robotic hepatectomy and to compare the outcomes of robotic hepatectomy and laparoscopic hepatectomy among different difficulty levels. METHODS: Clinical data from all consecutive patients who underwent robotic and conventional laparoscopic hepatectomy at the Prince of Wales Hospital, Hong Kong, were prospectively collected and reviewed. The difficulty level of operations was graded using the DSS. Perioperative outcomes of robotic and conventional laparoscopic hepatectomy were compared at each difficulty level. RESULTS: A total of 107 and 94 patients underwent robotic and laparoscopic hepatectomy during the study period, respectively. Among them, 16 and 2 patients were operated for recurrent pyogenic cholangitis, respectively, and were excluded because no mark for tumour location can be assigned. For robotic hepatectomy, a higher DSS was significantly correlated with higher minor complication rate (p = 0.001), more intraoperative blood loss (p = 0.002), longer operation time (p < 0.001) and longer post-operative hospital stay (p < 0.001). The mean DSS scores of robotic and laparoscopic hepatectomy were 4.5 and 3.6, respectively. (p = 0.004). For cases with low (DSS 1-3) and intermediate (DSS 4-6) difficulty level, there was no significant difference in operative blood loss, operation time and overall complications rate. Only 2 cases (2.2%) with high difficulty level were operated with laparoscopic approach while 20% of patients operated with robotic approach had DSS > 6. CONCLUSIONS: DSS significantly correlated with surgical outcomes in patient who underwent robotic hepatectomy. Perioperative outcomes following robotic and conventional laparoscopic hepatectomy were similar in cases with low and intermediate difficulty. However, robotic system allowed minimally invasive approach in cases with higher difficulty level.

Enhanced recovery after surgery for liver resection.

INTRODUCTION: Enhanced recovery after surgery (ERAS) reduces postoperative length of hospital stay and patient stress response to liver surgery. The aim of the present study was to evaluate the efficacy and feasibility of an ERAS programme for liver resection. METHODS: A multidisciplinary ERAS protocol was implemented for both open and laparoscopic liver resection in a tertiary hospital in Hong Kong. The clinical outcomes of patients who underwent liver resection and underwent the ERAS perioperative programme were compared with those who received a conventional perioperative programme between September 2015 and July 2016. Propensity score matching analysis was used to minimise background differences. RESULTS: A total of 20 patients who underwent liver resection were recruited to the ERAS programme. Their clinical outcomes were compared with another 20 patients who received hepatectomy under a conventional perioperative programme after propensity score matching. The ERAS programme was associated with a significantly shorter length of hospital stay (P=0.033) without an increase in complication rates in patients who underwent open liver resection. There was no such significant association in patients who underwent laparoscopic liver resection. No patients required readmission in this cohort. CONCLUSIONS: The ERAS perioperative programme for liver resection is safe and feasible. It significantly shortened the hospital stay after open liver resection but not after laparoscopic liver resection.

Comparative Analysis of Proteins with Stimulating Activity on Ovarian Estradiol Biosynthesis from Four Different Dioscorea Species in vitro Using Both Phenotypic and Target-based Approaches: Implication for Treating Menopause.

Rhizomes of Dioscorea species are traditionally used for relieving menopausal syndromes in Chinese medicine. The estrogen-stimulating bioactive principles have been demonstrated in our previous study. In this study, the estrogen-stimulating effects of proteins isolated from four Dioscorea species [D. alata L. (DA), D. zingiberensis C.H. Wright (DH), D. collettii var. hypoglauca (Palib.) S.J. Pei & C.T. Ting (DH), and D. oppositifolia L. (DO)] have been investigated and compared. Microscopic authentication of four Dioscorea species was performed by using paraffin and powder sections of the rhizomes. The potential bioactive proteins of four Dioscorea species have been rapidly isolated by using a DOI-antibody affinity column chromatography on immobilized antibodies against on estradiol-stimulating protein from DO (DOI), and their bioactivity has been rapidly confirmed and compared by phenotypic (i.e., estradiol-stimulating effect) and target-based (i.e., STAR, aromatase, estrogen receptors) screening approaches. The estrogen-stimulating activity of bioactive proteins from DO is the highest. In addition, bioactive proteins from DO upregulated the estradiol-metabolizing enzymes (aromatase and steroidogenic acute regulatory protein). Meanwhile, bioactive proteins from DA, DH and DO upregulated estrogen receptor ß (ERß). All bioactive proteins did not change the expression of estrogen receptor ß (ERα). The estrogen-stimulating bioactive proteins isolated from DO increased biosynthesis of estradiol and upregulated the protein expression of aromatase, steroidogenic acute regulatory protein, and ERß. The results scientifically support the traditional use of DO in Chinese medicine for relieving menopausal syndrome. Besides, proteins from DA and DZ could also upregulate the translational levels of ERß, and potentially reducing the risk of ovarian cancer, which also support the clinical use of them for treating female aging disorder. Graphical Abstract Comparative Analysis of DOI-like Proteins with Stimulating Activity on Ovarian Estradiol Biosynthesis from Four Different Dioscorea Species in vitro.

Antiviral therapy improves post-hepatectomy survival in patients with hepatitis B virus-related hepatocellular carcinoma: a prospective-retrospective study.

BACKGROUND: The effect of antiviral therapy on the post-hepatectomy long-term survival in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains uncertain. AIM: To evaluate the effect of antiviral therapy on post-hepatectomy survival and recurrence in patients with HBV-related HCC. METHODS: This was a prospective-retrospective study of a total of 404 patients who underwent hepatectomy for HBV-related HCC in a tertiary academic hospital. Data on patient and tumour characteristics, tumour recurrence, treatment for recurrence and survival were compared between antiviral and no antiviral groups. RESULTS: Patient's and tumour characteristics were comparable between the two groups, except a higher proportion of patients with cirrhosis in the antiviral group. With a mean follow-up time of 52.4 months, antiviral group had a better 5-year overall survival (66.7% vs. 56.0%, P = 0.001) while there was no significant difference in the 5-year disease-free survival (44.7% vs. 38.1%, P = 0.166). Use of antiviral therapy was associated with better liver function reserve at the time of recurrence and a greater proportion of patients could receive curative treatment for recurrence (38.5% vs. 24.3%, P = 0.041). There was no significant different in the hazard ratios of patients who started antiviral therapy before or after operation (P = 0.054). CONCLUSIONS: Use of antiviral therapy improves the long-term post-hepatectomy survival in patients with HBV-related HCC. With a better liver function reserve at the time of recurrence, a greater proportion of patients in antiviral group could receive curative treatment for recurrence.

An uncommon cause of Cushing's syndrome in a 70-year-old man.

Cushing's syndrome due to exogenous steroids is common, as about 1% of the general populations use exogenous steroids for various indications. Although endogenous Cushing's syndrome due to ectopic adrenocorticotropic hormone from a pancreatic neuroendocrine tumour is rare, a correct and early diagnosis is important. The diagnosis and management require high clinical acumen and collaboration between different specialists. We report a case of ectopic adrenocorticotropic hormone Cushing's syndrome due to pancreatic neuroendocrine tumour with liver metastasis. Early recognition by endocrinologists with timely surgical resection followed by referral to oncologists led to a favourable outcome for the patient up to 12 months after initial presentation.

Late presentation of simple virilising 21-hydroxylase deficiency in a Chinese woman with Turner's syndrome.

Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a well-known disorder of sexual development (previously known as ambiguous genitalia) in genotypic female neonates. We report on a 66-year-old Chinese, brought up as male, with a simple virilising form of congenital adrenal hyperplasia associated with Turner's syndrome (karyotype 45,X/47,XXX/46,XX). His late presentation was recognised due to his exceptionally short stature and persistent sexual ambiguity. His condition was only brought to medical attention as he developed a huge abdominal mass, which later turned out to be a benign ovarian mucinous cyst. It is therefore important to look out for co-existing congenital adrenal hyperplasia in patients with Turner's syndrome and virilisation, after the presence of Y chromosome material has been excluded.

Randomized clinical trial of open hepatectomy with or without intermittent Pringle manoeuvre.

BACKGROUND: The intermittent Pringle manoeuvre (IPM) is commonly applied during liver resection. Few randomized trials have addressed its effectiveness in reducing blood loss and the results have been conflicting. The present study investigated the hypothesis that IPM could reduce blood loss during liver resection by 50 per cent. METHODS: Between May 2008 and April 2011, patients who underwent elective open hepatectomy were randomized into an IPM or no Pringle manoeuvre (NPM) group and stratified according to the presence or absence of cirrhosis. Data on demographics, type of hepatectomy, operative blood loss, duration of operation, mortality, morbidity and postoperative liver function were recorded and analysed. The primary endpoint was operative blood loss. RESULTS: There were 63 patients in each group. Median (range) operative blood loss was 370 (50-3600) ml in the IPM group versus 335 (40-3160) ml in the NPM group (P = 1·000). There were no differences in blood loss in different phases of the operation, blood loss per area of liver transected or blood transfusion rate, nor in total duration of operation or liver transection time. Postoperative serum alanine aminotransferase levels were higher in the IPM group (P < 0·001). There were more postoperative complications in the IPM group (41 versus 24 per cent; P = 0·036). CONCLUSION: The IPM did not reduce blood loss, but was associated with raised levels of postoperative liver parenchymal enzymes and more complications. REGISTRATION NUMBER: NCT00730743 (http://www.clinicaltrials.gov).

Surgical ablation of hepatocellular carcinoma with 2.45-GHz microwave: a critical appraisal of treatment outcomes.

OBJECTIVE: To evaluate the efficacy and safety of a new generation of 2.45-GHz microwave to ablate hepatocellular carcinoma by surgical approach. DESIGN; Case series with prospective follow-up. SETTING: A university teaching hospital in Hong Kong. PATIENTS: From March 2009 to January 2011, 26 consecutive patients (19 men and 7 women) with a median age of 63 (range, 49-79) years with hepatocellular carcinoma were recruited. Five (19%) of the patients had recurrent hepatocellular carcinoma after previous treatment. INTERVENTION: Microwave ablation for hepatocellular carcinomas (one tumour, n=24; two tumours, n=2) using a laparoscopic (n=16) or open approach (n=10). MAIN OUTCOME MEASURES: Operative mortality and morbidity, rate of incomplete ablation, recurrence rate, and survival rate. RESULTS: The median tumour diameter was 3.8 cm (range, 2.0-6.0 cm). Complications occurred in five (19%) of the patients; only one was ablation-related, and there was no operative mortality. One (4%) of the patients experienced incomplete ablation. Recurrent tumours were noted in 11 (42%) of the patients (5 were local, 2 were remote, and 4 were multifocal) after a median follow-up of 14 (range, 4-26) months. The failure rate for local disease control was 23%, and was 14% if patients with recurrent hepatocellular carcinoma were excluded. All but one patient survived until the time of censorship. The mean survival was 25 (standard deviation, 1) months. CONCLUSION: This new-generation microwave technique is safe and effective for local ablation of hepatocellular carcinoma. It is a valuable treatment option for patients who are not candidates for hepatectomy.

Single-incision laparoscopic cholecystectomy: from four wounds to one.

OBJECTIVE: To review the initial results and surgical outcomes of single-incision laparoscopic cholecystectomy. DESIGN: Prospective case series. SETTING: A university teaching hospital and a regional hospital in Hong Kong. PATIENTS: All patients undergoing single-incision laparoscopic cholecystectomy from August 2009 to March 2011. RESULTS: Fifty patients underwent single-incision laparoscopic cholecystectomy during the study period. The indications for surgery included symptomatic gallstones (n=43) and gallbladder polyps (n=7). The mean operating time was 78 (standard deviation, 24) minutes. Forty-five of the patients successfully underwent single-incision laparoscopic cholecystectomy, giving a success rate of 90%. In the remaining five patients, additional working ports were constructed to obtain better exposure and dissection around Calot's triangle. On comparing the results of the initial 25 cases to the subsequent 25 cases, in the latter group the operating time was significantly shorter (86 vs 71 minutes; P=0.02), and the success rate was higher (80% vs 100%; P=0.05). During the median follow-up period of 6.8 months, four patients had complications, which included: postoperative urinary retention (n=2), one each with a haematoma and an incisional hernia. No patient endured bile duct injury, postoperative bile leakage, or haemorrhage in our series. CONCLUSION: Single-incision laparoscopic cholecystectomy is feasible and safe for treatment of uncomplicated gallbladder diseases. There was a reduction in the operating time and increase in success rate with accumulation of experience. Nevertheless, surgeons should be cautious about the potential risks of this new technique.

Meta-analysis: the efficacy of anti-viral therapy in prevention of recurrence after curative treatment of chronic hepatitis B-related hepatocellular carcinoma.

BACKGROUND: The role of anti-viral therapy in prevention of hepatocellular carcinoma (HCC) recurrence is to be defined. AIM: To investigate the role of anti-viral therapy in prevention of tumour recurrence after curative treatment of hepatitis B virus (HBV)-related HCC. METHODS: A systematic electronic search on keywords including HCC and different anti-viral therapies was performed through eight electronic databases, including Medline, EMBASE and Cochrane Databases. The primary outcome was HCC recurrence after curative treatment of HBV-related HCC. The secondary outcomes were mortality related to HCC, mortality related to liver failure and the overall mortality. RESULTS: Nine cohort studies were included with a total number of 551 patients: 204 patients with anti-viral treatment group and 347 patients without anti-viral treatment (control group). There was significant difference in the incidence of HCC recurrence in favour of the anti-viral treatment group (55% vs. 58%; odds risk (OR)=0.59, 95% CI 0.35-0.97, P=0.04). The risk of HCC was reduced by 41% in the anti-viral treatment group. There were also significant differences in favour of anti-viral treatment group in terms of liver-related mortality (0% vs. 8%; OR=0.13, 95% CI 0.02-0.69, P=0.02) and overall mortality (38% vs. 42%; OR=0.27, 95% CI 0.14-0.50, P<0.001). CONCLUSIONS: Anti-viral therapy has potential beneficial effects after the curative treatment of HBV-related hepatocellular carcinoma in terms of tumour recurrence, liver-related mortality and overall survival. Anti-viral therapy should be considered after curative treatment of hepatocellular carcinoma.

The analgesic efficacy of continuous wound instillation with ropivacaine after open hepatic surgery.

The analgesic efficacy of continuous local anaesthetic wound instillation after open hepatic surgery was evaluated. Forty-eight patients scheduled for elective liver surgery were assigned to receive either ropivacaine 0.25% or saline infusion at 4 ml.h(-1) for 68 h via two multi-orifice indwelling catheters placed within the musculo-fascial layer before skin closure; plasma ropivacaine concentrations were measured during the infusion. Supplemental analgesia was provided by intravenous patient-controlled analgesia morphine. Patients in the ropivacaine group had decreased mean (SD) total morphine consumption (58 (30) mg vs 86 (44) mg, p = 0.01) and less pain at rest as well as after spirometry at 4, 12, 24, 48 and 72 h postoperatively (p < 0.01). Forced vital capacity was reduced postoperatively in both groups, but the reduction was greater in the saline group at 12 and 24 h (p = 0.03). The mean plasma concentration of ropivacaine increased to 2.05 (0.78) µg.ml(-1) at the point when the infusion was terminated.

Phaeochromocytoma in the Hong Kong Chinese population.

OBJECTIVE: To review the clinical manifestations of phaeochromocytoma in a Hong Kong Chinese population. DESIGN: Retrospective review. SETTING. Five public hospitals in Hong Kong. PATIENTS: Seventeen patients with operated phaeochromocytoma between 1994 and 2003 were reviewed retrospectively. RESULTS: Six patients (35%) were men, 11 (65%) were women. The mean age at presentation was 47 (range, 17-72) years. The diagnosis post-presentation was delayed by 1 to 132 months. Over 70% of the patients had hypertension. The most frequent symptoms were headache (53%), palpitations (53%), and sweating (41%); all these symptoms were present in 24% of the patients. Four (24%) had hereditary phaeochromocytoma/paraganglioma syndrome. The sensitivity of 24-hour urinary catecholamine measurements was 82%. Mean urinary adrenaline and noradrenaline concentrations were respectively 7- and 8-fold greater than the upper reference limits. Computed tomography and metaiodobenzylguanidine scintigraphy were the most widely used means for tumour localisation (sensitivity, 100% and 87% respectively). Approximately 65% of the patients had intra-adrenal tumours; 53% were on right side, 18% were bilateral. All the patients were prescribed phenoxybenzamine (dosage range, 20-120 mg/day) preoperatively. Two thirds of the patients had improved blood pressure 1 year after the operation. No malignancy was reported after a mean follow-up period of 7 years. CONCLUSION: Our series of patients with phaeochromocytomas commonly had a high frequency of normotension and extra-adrenal tumours. A high index of clinical suspicion and appropriate biochemical investigations are necessary to make the diagnosis, especially for patients manifesting adrenal incidentaloma and extra-adrenal lesion.

Expression of the repulsive SLIT/ROBO pathway in the human endometrium and Fallopian tube.

We investigated whether the repulsive SLIT/ROBO pathway is expressed in the endometrium and is negatively regulated during implantation. We also examined whether deficient expression in the Fallopian tube (FT) may predispose to ectopic pregnancy (EP). Endometrium (n = 21) and FT (n = 17) were collected across the menstrual cycle from fertile women with regular cycles. Decidualized endometrium (n = 6) was obtained from women undergoing termination, and FT (n = 6) was obtained from women with EP. SLIT/ROBO expression was quantified by reverse transcription-PCR and protein localized by immunohistochemistry. The regulation of SLIT/ROBO expression in vitro, by sex steroids and hCG, was assessed in endometrial (hTERT-EEpC) epithelial cells, and the effects of Chlamydia trachomatis infection and smoking were studied in oviductal (OE-E6/E7) epithelial cells. Endometrial SLIT3 was highest in the mid-secretory phase (P = 0.0003) and SLIT1,2 and ROBO1 showed a similar trend. ROBO2 was highest in proliferative phase (P = 0.027) and ROBO3,4 showed a similar trend. SLIT2,3 and ROBO1, 4 were lower in decidua compared with mid-secretory endometrium (P < 0.05). SLITs and ROBOs, excepting ROBO2, were expressed in FT but there were no differences across the cycle or in EP. SLIT/ROBO proteins were localized to endometrial and FT epithelium. Treatment of hTERT-EEpC with a combination of estradiol and medroxyprogesterone acetate inhibited ROBO1 expression (P < 0.01) but hCG had no effect. Acute treatment of OE-E6/E7 with smoking metabolite, cotinine, and C. trachomatis had no effect. These findings imply a regulated role for the endometrial SLIT/ROBO interaction during normal development and pregnancy but that it may not be important in the aetiology of EP.

Radiofrequency ablation for 110 malignant liver tumours: preliminary results on percutaneous and surgical approaches.

BACKGROUND: Radiofrequency ablation (RFA) has been widely applied for the treatment of hepatocellular carcinoma and liver metastases. The reported mortality and morbidity rates are low. The aim of this study is to evaluate the safety and efficacy of RFA, and compare the results performed percutaneously versus surgically. PATIENTS AND METHODS: From 2003 to 2006, 79 patients with hepatic malignancies (59 hepatocellular carcinoma, 20 liver metastases) with a total of 110 lesions underwent RFA in our centre. Postablation assessment by CT scan was performed in all patients at 1-, 3- and 6-month intervals. Post-procedural complications, recurrence and survival were analysed. RESULTS: The patients' mean age was 60.0 years. In 46.8% of cases, we used a percutaneous approach; in 53.2% of cases, a surgical approach (8.9% laparoscopic; 44.3% open) was used if percutaneous approach was not feasible. The mean tumour size was 2.4 cm. Within the surgical group, 69% of patients received concomitant operative procedures such as cholecystectomy and hepatectomy. No treatment-related mortality was observed. Immediate complications occurred in five patients (6.3%), including gastric serosal burn (n = 1), ground pad superficial skin burn (n = 1), intra-abdominal bleeding (n = 2) and pleural effusion (n = 1). All patients except one attended subsequent follow-up, with a mean period of 16 months. Ablation was considered complete in 82.3% of patients (percutaneous approach 81.1%, surgical approach 83.3%, p = 0.72). Intrahepatic recurrence was observed in 52.3%, the majority of them located away from the RFA site. Extrahepatic recurrences were observed in 16.9% (percutaneous approach 16.7%, surgical approach 17.1%, p = 0.76). The overall one- and two-year survival rate was 93.7% and 74.4% respectively, and no statistically significant difference was observed between the two approaches. CONCLUSION: RFA is a safe and effective procedure for treating patients with malignant liver tumours. No difference in short term outcomes was observed between percutaneous and surgical approaches. A more prolonged follow-up study is required to assess longer-term outcomes.

Dilated common bile ducts mimicking choledochal cysts in ketamine abusers.

Substance abuse is a major health and social problem among Hong Kong youth and ketamine is the drug most commonly abused. Ketamine abuse is associated with a series of side-effects that include hallucination, nausea, vomiting, elevation of blood pressure, and urinary bladder dysfunction. Here we report three cases of ketamine abuse in which the abusers presented with recurrent epigastric pain and dilated common bile ducts that mimicked choledochal cysts on imaging. The dilated biliary tree may occur more frequently than was once assumed.